Abstract This proposal requests funds to purchase a Q-Exactive Plus mass spectrometer to be housed in an active and successful officially designated UC Davis Campus Research Core Facility, the Campus Mass Spectrometry Facilities (CMSF). A high resolution mass spectrometry instrument is requested to support 16 NIH- funded research projects (7 Major Users) focused on novel and emerging therapeutics. These projects range from advanced imaging molecules for immunotherapy, theranostics for prostate cancer, and therapeutic targeting agents for ovarian cancer. Discovery of new therapeutics requires access to high performance capabilities of modern mass spectrometers that provide higher resolution, reliable MS/MS methods, improved sensitivity and good throughput. The Thermo Q-Exactive Plus mass spectrometer will serve the increasing number of samples of our Major Users that is currently stressing an 12-year old LTQ Orbitrap mass spectrometer. The LTQ-Orbitrap was purchased with an NIH SIG award and has been successfully maintained for 12 years. However, the age and the popularity of the older instrument impacts our Major User?s access, and its technological limitations no longer meet the methodological demands of our Major Users. Together, these constraints are hampering the progress of NIH- funded projects in their laboratories as well as those efforts of their collaborators. The Q-Exactive Plus, with its enhanced sensitivity, better robustness, HCD MS/MS capabilities with no low mass cutoff, overall greater mass accuracy, high resolution and enhanced precursor ion selection, as well as a modern operating system, will significantly advance our Major Users pursuits of novel therapeutics and drug discovery with significantly improved data. UC Davis is strongly committed to supporting its campus-wide mass spectrometry core and is supporting this proposal with a substantial match. We plan to integrate this instrument into an existing UC Davis Campus Research Core Facility, the CMSF, which is maintained by the institution with significant infrastructure and oversight and advisory committees. The existing infrastructure will integrate the operation, maintenance and management of the proposed instrument which will, in turn, stimulate new research projects and innovations for many years. !